This invention relates to polymers containing poly(vinyl pyrrolidone) copolymerized with other polymers such as polyurethanes, etc. Such materials are particularly useful as biomaterials in medical devices.
The chemistry of block copolymers is extensive and well developed. They can be used to combine the properties of different polymers in one material. For example, a polymer having hydrophilic properties can form one block and a polymer having hydrophobic properties can form another block. Thus, one material can have combinations of properties that neither constituent polymer possesses alone. This can be of significant utility in the medical device arena.
Polymers used to create medical devices are typically chosen for their bulk properties; however, it is often desirable for the surfaces of such medical devices to possess different properties than that of the bulk polymer. For example, it may be desirable for a polymer surface to have a different level of compatibility with other polymers or tissues, surface energy, etc., than that of the bulk polymer. Thus, block copolymers are desirable materials to investigate for their utility in modifying polymer surfaces for medical device applications.
Block copolymers have been used to modify polyurethane surfaces, which are important biomedical polymers used in implantable devices such as artificial hearts, cardiovascular catheters, pacemaker lead insulation, etc. Such block copolymers have been used to enhance antimicrobial properties, lubricity, barrier properties, anticoagulant properties, and the like. For example, U.S. Pat. No. 4,675,361 (Ward, Jr.) discloses a block copolymer for improved biocompatibility. Also, U.S. Pat. No. 5,302,385 (Khan et al.) discloses a polyurethane-poly(vinyl pyrrolidone) copolymer foam having antimicrobial properties coated on a catheter. The resultant polymer is highly branched or a network polymer without a well-defined or controllable block architecture.
Other block copolymers are needed for modifying the surface properties of medical devices.
The present invention relates to block copolymers, particularly AnB block copolymers, wherein n is at least two, and more particularly A-B-A block (triblock) copolymers, that include poly(vinyl pyrrolidone) in the A blocks, and urethane groups, urea groups, amide groups, imide groups, ester groups, ether groups, or combinations thereof (e.g., polyurethanes, polyureas, or polyurethane-ureas) in the B block. This includes methods for making such polymers.
The block copolymers of the present invention are particularly useful as biomaterials in medical devices. Certain preferred embodiments of the block copolymers can also provide a lubricious surface (e.g., a slip coating on a polymeric surface). Lubricous surfaces are desirable for many medical devices, particularly the inner surfaces of lead delivery catheters. Coating conventional materials on the inner surfaces of such catheters can be difficult and expensive, however. The block copolymers of the present invention provide an opportunity to more easily manufacture such devices. Methods involving dip coating followed by solvent removal techniques can be used to apply the block copolymers of the present invention to a substrate. Alternatively, the block copolymers can be coextruded with another thermoplastic polymer to form a layered construction. Extrusion methods can also involve reactive coextrusion.
In one embodiment, the present invention provides a thermoplastic AnB block copolymer, wherein the A blocks include poly(vinyl pyrrolidone) units and the B block is a long-chain organic connecting unit that includes urethane groups, urea groups, imide groups, amide groups, ether groups, or combinations thereof, wherein n is at least two.
The present invention provides medical devices. One such device includes a surface that includes a thermoplastic AnB block copolymer, wherein the A block includes poly(vinyl pyrrolidone) units and the B block is a long-chain organic connecting unit that includes urethane groups, urea groups, imide groups, amide groups, ester groups, ether groups, or combinations thereof, wherein n is at least two. The xe2x80x9csurfacexe2x80x9d can be the surface of a coating, for example, of a thermoplastic AnB block copolymer on another substrate, such as a polymeric material. Alternatively, the xe2x80x9csurfacexe2x80x9d can be the surface of an extruded layer, for example, of a thermoplastic AnB block copolymer, which can be coextruded with another polymeric material, or formed using reactive coextrusion.
The present invention also provides methods of modifying a surface of a medical device. One method includes: preparing a thermoplastic AnB block copolymer, wherein the A block includes poly(vinyl pyrrolidone) units and the B block is a long-chain organic connecting unit that includes urethane groups, urea groups, imide groups, amide groups, ether groups, ester groups, or combinations thereof, wherein n is at least two; and applying the AnB copolymer to the surface of the medical device.
The present invention also provides methods of preparing a thermoplastic AnB block copolymer. One method includes reacting a substantially monofunctional poly(vinyl pyrrolidone) with a functionalized B-block precursor that includes functional groups reactive with the functional groups of the poly(vinyl pyrrolidone) to form the thermoplastic AnB block copolymer. In an alternative method, the block copolymer is made in one step using a substantially monofunctional poly(vinyl pyrrolidone) with reactants for the functionalized B-block precursor.
As used herein, the term xe2x80x9corganic groupxe2x80x9d refers to a hydrocarbyl group (aliphatic and/or aromatic) optionally including other atoms (e.g., heteroatoms) or groups (e.g., functional groups) replacing the carbon and/or hydrogen atoms. The term xe2x80x9caliphatic groupxe2x80x9d means a saturated or unsaturated linear (i.e., straight chain), cyclic, or branched hydrocarbon group. This term is used to encompass alkyl (e.g., xe2x80x94CH3) (or alkylene if within a chain such as xe2x80x94CH2xe2x80x94), alkenyl (or alkenylene if within a chain), and alkynyl (or alkynylene if within a chain) groups, for example. The term xe2x80x9calkyl groupxe2x80x9d means a saturated linear or branched hydrocarbon group including, for example, methyl, ethyl, isopropyl, t-butyl, heptyl, dodecyl, octadecyl, amyl, 2-ethylhexyl, and the like. The term xe2x80x9calkenyl groupxe2x80x9d means an unsaturated, linear or branched hydrocarbon group with one or more carbon-carbon double bonds, such as a vinyl group. The term xe2x80x9calkynyl groupxe2x80x9d means an unsaturated, linear or branched hydrocarbon group with one or more carbon-carbon triple bonds. The term xe2x80x9caromatic groupxe2x80x9d or xe2x80x9caryl groupxe2x80x9d means a mono- or polynuclear aromatic hydrocarbon group. These hydrocarbon groups may be substituted with heteroatoms, which can be in the form of functional groups. The term xe2x80x9cheteroatomxe2x80x9d means an element other than carbon (e.g., nitrogen, oxygen, sulfur, chlorine, etc.).
As used herein, the terms xe2x80x9ca,xe2x80x9d xe2x80x9can,xe2x80x9d xe2x80x9cone or more,xe2x80x9d and xe2x80x9cat least onexe2x80x9d are used interchangeably.
As used herein, a xe2x80x9cthermoplasticxe2x80x9d polymer is one that will melt and flow when heated and reform substantially the same material upon cooling.
As used herein, a xe2x80x9cbiomaterialxe2x80x9d or xe2x80x9cbiocompatible materialxe2x80x9d may be defined as a material that is substantially insoluble in body fluids and tissues and that is designed and constructed to be placed in or onto the body or to contact fluid or tissue of the body. Ideally, a biocompatible material will not induce undesirable reactions in the body such as blood clotting, tissue death, tumor formation, allergic reaction, foreign body reaction (rejection) or inflammatory reaction; will have the physical properties such as strength, elasticity, permeability, and flexibility required to function for the intended purpose; can be purified, fabricated, and sterilized easily; and will substantially maintain its physical properties and function during the time that it remains implanted in or in contact with the body.
As used herein, a xe2x80x9cmedical devicexe2x80x9d may be defined as an article that has surfaces that contact blood or other bodily tissues in the course of their operation. This can include, for example, extracorporeal devices for use in surgery such as blood oxygenators, blood pumps, blood sensors, tubing used to carry blood, and the like, which contact blood, which is then returned to the patient. This can also include implantable devices such as vascular grafts, stents, electrical stimulation leads, heart valves, orthopedic devices, catheters, guide wires, shunts, sensors, replacement devices for nucleus pulposus, cochlear or middle ear implants, intraocular lenses, and the like.